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Implementing And Enhancing Evidence-based Research And Practice In Hepatology
Funder
National Health and Medical Research Council
Funding Amount
$569,219.00
Summary
The overall aim of this proposal is to tackle unmet challenges in liver disease research. This will be achieved through (a) Population level programs to deliver new treatments for patients with hepatitis C; (b) Developing integrated care models to treat hepatitis B; (c) Developing population-level programs for liver cancer control; and (d) Identification of patients at risk of severe liver disease through understanding the genetic basis of disease progression.
Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
ANTIVIRAL DRUG RESISTANT HBV: PATHOGENIC AND ONCOGENIC SIGNIFICANCE OF THE ALTERED VIRAL ENVELOPE
Funder
National Health and Medical Research Council
Funding Amount
$509,284.00
Summary
We aim to investigate the consequences of long-term therapy for hepatitis B on liver cancer progression. We propose that antiviral therapy is associated with persistent expression and accumulation of potentially oncogenic surface proteins in the liver. This can dramatically alter the viral lifecycle, particularly the HBsAg secretion pathway, which can cause serious effects in the host hepatocyte biology, including promoting pathways to tumour formation.
Protein Topogenesis And The Assembly/disassembly Of The Enveloped Hepatitis B Virus.
Funder
National Health and Medical Research Council
Funding Amount
$197,884.00
Summary
An estimated 350 million people worldwide, and 250,000 in Australia, are chronically infected with the hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current treatments are inadequate. A major obstacle to the study of this virus is the lack of a cell culture infection system. We have used the duck hepatitis B virus (DHBV) model to study the events leading up to assembly of the virus in ....An estimated 350 million people worldwide, and 250,000 in Australia, are chronically infected with the hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current treatments are inadequate. A major obstacle to the study of this virus is the lack of a cell culture infection system. We have used the duck hepatitis B virus (DHBV) model to study the events leading up to assembly of the virus in a way which prepares the viral envelope or outer coat for its foray into a new host cell. The project will examine the specific interactions of two proteins, the large and the small envelope protein, in addition to a third envelope protein we have recently discovered, which together make up the viral envelope. This will reveal which envelope components are required to make up the specific structures known to be essential for the disruption of the host cell membrane and subsequent entry of the virus to a new cell. An understanding of the changes that occur to the viral envelope upon entry will enable development of strategies for the inhibition or blocking of this change, thus identifying targets for the development of new antiviral agents. Because HBV is just one of many viruses which have an envelope, all of which must enter the cell in some way, our studies of HBV will also provide new clues with respect to the replication of other viruses such as measles, influenza and HIV. A related part of the study will examine the orientation of the large envelope protein within the virus particle and how it changes its orientation to assume its many important functional roles, in the late stages of particle assembly. Expanding on our finding that the small protein is essential to the orientation of the large protein, this study will reveal the mechanism of a unique method of protein transport which may have wider implications in cell biology.Read moreRead less
Novel Bioinformatic Methods To Determine The Link Between Genomic Complexity Of Hepatitis Viruses And Liver Disease Phenotypes
Funder
National Health and Medical Research Council
Funding Amount
$605,859.00
Summary
Bioinformatics is a discipline concerned with the study of how information is stored and used in biological systems. Here we develop bioinformatic tools to study how hepatitis viruses evolve during an infection and how these infections cause severe liver diseases.
Despite recent advances in therapeutic options, chronic viral infections, including infection with hepatitis C virus and hepatitis B virus, continue to be a significant cause of morbidity and mortality in Australia and affecting hundreds of millions of people worldwide. This R&D program aims to develop a cheaper drug formulation that is easier to deliver and more stable for transport to remote areas.
A New Insight Into Hepatitis B Infection:the HBV Fusion Peptide
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Three hundred and fifty million people worldwide and 250,000 in Australia are chronically infected with hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current therapies are inadequate. New antiviral treatments requiring the identification of new antiviral targets are needed to combat the disease but a major obstacle to the study of HBV is the lack of a cell culture system. As a result n ....Three hundred and fifty million people worldwide and 250,000 in Australia are chronically infected with hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current therapies are inadequate. New antiviral treatments requiring the identification of new antiviral targets are needed to combat the disease but a major obstacle to the study of HBV is the lack of a cell culture system. As a result nothing is known about how HBV enter and fuses with the host liver cell but we have made significant progress with the identification of the entry and fusion events of the related duck hepatitis B virus, using the duck infection model. This knowledge is now ready for application to the medically important HBV by use of primary human liver cells and the techniques developed in the duck hepatitis B virus model.Read moreRead less
A Study Of The Relationship Between Vitamin D Status And The Severity And Outcomes Of Chronic Non-cholestatic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Vitamin D deficiency is associated with common and severe conditions such as cancer, cardiovascular disease, autoimmune disease and diabetes. Recent studies suggest that vitamin D deficiency also worsens the severity and prognosis of chronic liver disease and that vitamin D replacement may improve outcomes. This research will further investigate the relationship of vitamin D deficiency to liver disease caused by the common conditions hepatitis B and C and non-alcoholic fatty liver disease and th ....Vitamin D deficiency is associated with common and severe conditions such as cancer, cardiovascular disease, autoimmune disease and diabetes. Recent studies suggest that vitamin D deficiency also worsens the severity and prognosis of chronic liver disease and that vitamin D replacement may improve outcomes. This research will further investigate the relationship of vitamin D deficiency to liver disease caused by the common conditions hepatitis B and C and non-alcoholic fatty liver disease and the impact of vitamin D replacement.Read moreRead less
The Role Of Stellate Cells In Fibrosis And Liver Disease Progression In HIV-Hepatitis B Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$157,292.00
Summary
Liver related mortality is the commonest cause of non-AIDS death in HIV infected individuals on treatment. With HIV, HBV liver damage is accelerated and liver-related mortality increased. Understanding how and why is critical to management. I will examine the role of hepatic stellate cells using in vitro models and directly ex vivo from infected patient biopsy tissue. I will investigate the activated of these cells by HIV and HBV infection, thus promoting scar formation with liver injury.
Worldwide >360 million people have chronic hepatitis B virus (HBV) infection that imparts a 25% lifetime risk of death due to serious liver disease. Current therapies for chronic HBV reduce levels of virus replication but fail to target the stable, nuclear episome, covalently closed circular DNA (cccDNA). The current study will determine what is required to eliminate cccDNA and how current therapies for chronic HBV infection should be modified to achieve this aim.